GVV858 alone or with fulvestrant or letrozole for HR+/HER2- breast cancer and other advanced tumors
An Open-label, Multi-center, Phase I/II Study of GVV858 as a Single Agent and in Combination With Endocrine Therapy in Patients With Advanced Hormone Receptor Positive, HER2- Negative Breast Cancer and Other Advanced Solid Tumors
This trial tests whether GVV858 alone or with fulvestrant or letrozole can help adults with HR+/HER2- advanced breast cancer, CCNE1‑amplified solid tumors, or metastatic castration‑resistant prostate cancer.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 205 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Novartis Industry-sponsored |
| Drugs / interventions | chemotherapy |
| Locations | 5 sites (Nashville, Tennessee and 4 other locations) |
| Trial ID | NCT07288359 on ClinicalTrials.gov |
What this trial studies
This first-in-human, open-label Phase I/II trial gives GVV858 as a single agent and in combination with fulvestrant or letrozole across several advanced cancer cohorts. Phase I uses dose-escalation with possible expansion cohorts to define safety, tolerability, and a recommended dose for further study. A combination arm may proceed into a randomized, open-label Phase II with optional dose optimization specifically in HR+/HER2- advanced breast cancer. Efficacy signals will be explored alongside safety, with expansion cohorts stratified by disease type and CCNE1 amplification where applicable.
Who should consider this trial
Good fit: Ideal candidates are adults with HR+/HER2- advanced breast cancer who progressed after endocrine therapy plus a CDK4/6 inhibitor and additional systemic therapy, patients with advanced solid tumors harboring CCNE1 amplification, or men with metastatic castration‑resistant prostate cancer meeting the trial's prior-therapy limits.
Not a fit: Patients with early-stage disease, tumors without CCNE1 amplification for the targeted cohorts, those with a neuroendocrine component in prostate cancer, or those who do not meet the prior-therapy requirements are unlikely to benefit from this early-phase trial.
Why it matters
Potential benefit: If successful, GVV858 could provide a new targeted treatment option that slows tumor growth for patients with HR+/HER2- breast cancer or CCNE1‑amplified tumors and potentially extend progression-free survival.
How similar studies have performed: Combining targeted agents with endocrine therapy has improved outcomes in HR+/HER2- breast cancer (for example CDK4/6 inhibitors), but GVV858 is first-in-human and its specific approach has not yet been proven in patients.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥ 18 years old. * Patients with one of the following histologically or cytologically confirmed advanced cancers: Phase I (patients with one of the following cancers, from whom no standard therapy is available or appropriate in the judgment of the investigator): * HR+/HER2- advanced breast cancer (aBC) with disease progression on or following at least one line of hormone-based therapy in combination with a CDK4/6i and at least one additional line of systemic therapy for metastatic disease. * Locally advanced or metastatic cancer with a CCNE1 amplification. For dose expansion only: no more than 3 prior lines of therapy for advanced or metastatic disease. * Metastatic castration-resistant prostate adenocarcinoma, with no documented neuroendocrine component, castrate level of testosterone, and no more than 3 prior lines of systemic therapy for metastatic disease. Phase II: * HR+/HER2- aBC with disease progression on or after an endocrine therapy in combination, with a CDK4/6 inhibitor for advanced disease with no more than 2 lines of endocrine therapy and no prior cytotoxic chemotherapy or antibody-drug-conjugate for advanced disease. \- Measurable disease as determined by RECIST v1.1. * BC only: If no measurable disease is present, then at least one predominantly lytic bone lesion must be present that can be accurately assessed at baseline and is suitable for repeated assessment. * metastatic Castration-Resistant Prostate Cancer (mCRPC) only: If no measurable disease is present per PCWG3 modified RECIST, then at least 1 metastatic lesion must be present on bone scan imaging. Exclusion Criteria: * Patients with inadequate bone marrow and/or organ functions with out-of-range laboratory values. * Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including myocardial infarction (MI), coronary artery bypass graft (CABG), long QT syndrome, or risk factors for Torsades de Pointes (TdP). * Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local therapy or increasing doses of corticosteroids within 2 weeks prior to study entry. * Patients with symptomatic visceral disease, including visceral crisis. * For patients with BC: Patient is concurrently using hormone replacement therapy. * Women of childbearing potential who are unwilling to use highly effective contraception methods, pregnant or nursing women. Other protocol-defined inclusion/exclusion criteria may apply.
Where this trial is running
Nashville, Tennessee and 4 other locations
- Tennessee Oncology PLLC — Nashville, Tennessee, United States (Recruiting)
- Novartis Investigative Site — Odense C, Denmark (Recruiting)
- Novartis Investigative Site — Kyoto, Japan (Recruiting)
- Novartis Investigative Site — Singapore, Singapore (Recruiting)
- Novartis Investigative Site — Taipei, Taiwan (Recruiting)
Study contacts
- Study coordinator: Novartis Pharmaceuticals
- Email: novartis.email@novartis.com
- Phone: 1-888-669-6682
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.